CN110437192A - A kind of compound, composition, preparation method and its usage for extracting from Spongia and belonging to sponge - Google Patents
A kind of compound, composition, preparation method and its usage for extracting from Spongia and belonging to sponge Download PDFInfo
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- CN110437192A CN110437192A CN201910698386.0A CN201910698386A CN110437192A CN 110437192 A CN110437192 A CN 110437192A CN 201910698386 A CN201910698386 A CN 201910698386A CN 110437192 A CN110437192 A CN 110437192A
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- A—HUMAN NECESSITIES
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- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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Abstract
The invention discloses a kind of Spongia that extracts to belong to the compound or its pharmaceutically acceptable salt of sponge, and discloses preparation method and belong to the compound of sponge or the composition of its pharmaceutically acceptable salt from Spongia containing said extracted；The invention also discloses said extracted from Spongia belong to sponge compound or its pharmaceutically acceptable salt, and combinations thereof be used to prepare application in anti-inflammatory drug and/or anticancer drug.The compound for extracting from Spongia category sponge of the invention is microbe-derived compound, has anti-inflammatory and anticancer activity, can be used for preparing anti-inflammatory drug or anticancer drug.
Description
Technical field
The invention belongs to natural products drug fields, and in particular to a kind of chemical combination for extracting from sponge Spongia sp.
Object, composition, preparation method and its usage.
Background technique
Ocean accounts for about the 71% of earth surface product, and biological capacity accounts for earth total capacity 80%, and ocean is not only the earth
The Source of life of all things on earth is also that biology saves most complete, the most abundant natural products resource treasure-house of resource.Due to marine ecology ring
The particularity (with high salt, high pressure anoxic, is protected from light, high temperature or low temperature) in border causes marine organisms and terrestrial life secondary metabolite
Biosynthesis pathway and reaction system have very big otherness, so that ocean secondary metabolite and terrestrial life secondary metabolism
Product, which is compared, bigger Chemical Diversity.Struggle for existence is extremely fierce between marine organisms species, brings up many marine organisms
Generate the secondary metabolite of some unique structures, diverse biological activities in evolutionary process, in favor of its existence, breeding, competition,
Information transmitting, the attachment resisted biological formidable opponent, avoid planktonic organism repair injured organism or keep its local living space
Independence, living marine resources become the important treasure-house of natural active compound.Natural conditions are often more severe, such as high in ocean
Press with high salt etc., marine microorganism can generate corresponding biological active agents constantly to ensure that it is above-mentioned that itself can be better adapted to
Condition.But it is relatively fewer for the research of sponge at present.Further to find new drug isoreactivity lead compound, applicant passes through
Various active screening and tracking, it was found that extract from Spongia belong to sponge, with anti-inflammatory, anti-tumor activity compound.
Summary of the invention
It is an object of the present invention to provide it is a kind of extract from Spongia belong to sponge, have anti-inflammatory and anti-tumor activity
Compound or its pharmaceutically acceptable salt, specific technical solution it is as follows: it is a kind of extract from Spongia belong to sponge compound
Or its pharmaceutically acceptable salt, shown in structural formula such as formula (I):
In formula,
R1The C for indicating H, optionally replacing1-C14Alkyl, the C optionally replaced1-C14Alkylthio group, the C optionally replaced1-C14Alcoxyl
Base or C1-C14Alkenyl；
R2The C for indicating H, optionally replacing1-C14Alkyl, the C optionally replaced1-C14Alkylthio group, the C optionally replaced1-C14Alcoxyl
Base or C1-C14Alkenyl；
R3The C for indicating H, optionally replacing1-C14Alkyl, the C optionally replaced1-C14Alkylthio group, the C optionally replaced1-C14Alcoxyl
Base or C1-C14Alkenyl；
R4The C for indicating H, optionally replacing1-C14Alkyl, the C optionally replaced1-C14Alkylthio group, the C optionally replaced1-C14Alcoxyl
Base or C1-C14Alkenyl；
Further, in formula (I), R1Indicate H, C1-C14Alkyl, halogenated C1-C14Alkyl, C1-C14Alkylthio group, halogenated C1-
C14Alkylthio group, C1-C14Alkoxy, halogenated C1-C14Alkoxy or C1-C14Alkenyl；
R2Indicate H, C1-C14Alkyl, halogenated C1-C14Alkyl, C1-C14Alkylthio group, halogenated C1-C14Alkylthio group, C1-C14Alcoxyl
Base, halogenated C1-C14Alkoxy or C1-C14Alkenyl；
R3Indicate H, C1-C14Alkyl, halogenated C1-C14Alkyl, C1-C14Alkylthio group, halogenated C1-C14Alkylthio group, C1-C14Alcoxyl
Base, halogenated C1-C14Alkoxy or C1-C14Alkenyl；
R4Indicate H, C1-C14Alkyl, halogenated C1-C14Alkyl, C1-C14Alkylthio group, halogenated C1-C14Alkylthio group, C1-C14Alcoxyl
Base, halogenated C1-C14Alkoxy or C1-C14Alkenyl；
Further, in formula (I), R1Indicate H, C1-C6Alkyl, C1-C6Alkylthio group, C1-C6Alkoxy or C1-C6Alkenyl；
R2Indicate H, C1-C6Alkyl, C1-C6Alkylthio group, C1-C6Alkoxy or C1-C6Alkenyl；R3Indicate H, C1-C6Alkyl, C1-C6Alkane sulphur
Base, C1-C6Alkoxy or C1-C6Alkenyl；R4Indicate H, C1-C6Alkyl, C1-C6Alkylthio group, C1-C6Alkoxy or C1-C6Alkene
Base；
Preferably, R1、R2、R3、R4It is each independently selected from H, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl
Base, sec-butyl, tert-butyl, vinyl；
Further, formula (I) structure is as follows:
Further, formula (I) is (+)-(I) or (-)-(I), and (+)-(I), (-)-(I) structure are as follows:
Further, formula (I) is the raceme of (+)-(I) and (-)-(I).
The invention also discloses extracting from as described above, Spongia belongs to the compound of sponge or its is pharmaceutically acceptable
The preparation method of salt belongs to sponge to Spongia with solvent and extracts, obtained extract is separated with column chromatography method, passes through
Elution, post-processing obtain the compound for extracting from Spongia and belonging to sponge；
Further, specific steps are as follows: cold soaking is carried out to Spongia category sponge with 95% ethyl alcohol and extracts to obtain crude extract,
It is successively carried out that each polar fraction extract, chloroform extract silicon is obtained by extraction with petroleum ether, chloroform, n-butanol after being suspended with water
Plastic column chromatography, and with chloroform/methanol carry out gradient elution, obtain 8 fractions (fraction 1~8)；Fraction 7 is with silicagel column through chlorine
Imitative/methanol affords 4 fractions (fraction 7-1~7-4), compound of formula I is isolated from fraction 7-1, and use chiral high performance
Liquid chromatography isolated (+)-(I) and (-)-(I).
In the definition of above compound structural formula, used technical term all has following meaning:
C1-C14Alkyl: carbon atom number be 1-14 linear or branched alkyl group, such as methyl, ethyl, propyl, isopropyl or
Tert-butyl；
C1-C14Alkoxy: carbon atom number is the linear or branched alkyl group of 1-14, is keyed in structure through oxygen atom；
C1-C14Alkylthio group: carbon atom number is the linear or branched alkyl group of 1-14, is keyed in structure through sulphur atom；
C1-C14 alkenyl: carbon atom number is the straight-chain alkenyl of 1-14, such as vinyl；
Optionally replace: being replaced by any substituent group as group.
The pharmaceutically acceptable salt can be the of the invention compound and chemistry that extract from Spongia and belong to sponge
Upper acceptable acid carries out reacting salt obtained, wherein chemically acceptable acid can be inorganic acid (such as hydrochloric acid, sulfuric acid, nitre
Acid or hydrobromic acid etc.) or organic acid (such as acetic acid, propionic acid, malonic acid, butyric acid, lactic acid, methanesulfonic acid, ethanesulfonic acid, benzene sulfonic acid, to first
Benzene sulfonic acid, maleic acid, benzoic acid, succinic acid, picric acid, tartaric acid, citric acid, fumaric acid etc.)；Described is pharmaceutically acceptable
Salt may be of the invention to extract from that Spongia belongs to the compound of sponge and chemically acceptable alkali carries out reacting obtained
Salt, wherein chemically acceptable alkali can be inorganic base (such as sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium carbonate, carbon
Sour potassium, sodium bicarbonate or saleratus) or organic base (such as trimethylamine, triethylamine, pyridine)；
Further, the pharmaceutically acceptable salt can be sylvite, sodium salt, ammonium salt, calcium salt, pyridiniujm or choline
Salt.
Extracting Spongia used in compound of the present invention to belong to sponge is 2016 from Chinese Zhanjiang, Guangdong Province
Acquisition, it is identified through Ji'nan University professor Xu Shihai.Preservation sample (number: 2016-05A) deposits in Guangzhou, Guangdong Province, China
Ji'nan University, city chemistry and Materials Academy department of chemistry.
It is a further object to provide a kind of anti-inflammatory and/or anticancer pharmaceutical compositions comprising formula (I) and/
Or (+)-(I) and/or (-)-(I) compound represented or its pharmaceutically acceptable salt and pharmaceutically acceptable carrier.
The amount of the active ingredient (i.e. the compounds of this invention) contained in pharmaceutical composition in one embodiment can root
It is specifically applied according to the case where state of an illness of patient, diagnosis, the amount or concentration of reactive compound are in a wider model
Interior adjusting is enclosed, in general, the weight range of reactive compound is the 1%~90% of composition weight；Preferably, reactive compound
Weight range is the 1%~20% of composition weight.
Although the compound of the present invention can be directly administered without any preparation, the various compounds preferably with
Pharmaceutically acceptable auxiliary material is prepared into pharmaceutical preparation use.Pharmaceutically acceptable auxiliary material includes diluent, lubricant, bonding
Agent, disintegrating agent, stabilizer, solvent etc..
Diluent of the present invention includes but is not limited to starch, microcrystalline cellulose, sucrose, dextrin, lactose, Icing Sugar, grape
Sugar etc.；The lubricant includes but is not limited to magnesium stearate, stearic acid, sodium chloride, enuatrol, sldium lauryl sulfate, Bo Luosha
Mother etc.；Described adhesive includes but is not limited to water, ethyl alcohol, starch slurry, syrup, hydroxypropyl methyl cellulose, carboxymethyl cellulose
Sodium, sodium alginate, polyvinylpyrrolidone etc.；The disintegrating agent include but is not limited to starch effervescent mixture i.e. sodium bicarbonate and
Citric acid, tartaric acid, low-substituted hydroxypropyl cellulose etc.；The stabilizer include but is not limited to polysaccharide for example acacin, agar,
Alginic acid, cellulose ether and carboxymethyl crusta ester etc.；The solvent includes but is not limited to water, salting liquid of balance etc..
In one embodiment, the pharmaceutical preparation includes oral preparation and ejection preparation.
In one embodiment, the oral preparation is solid orally ingestible, liquid oral medicine, and pharmacy is acceptable
Oral agents solid pharmaceutical preparation include, but are not limited to conventional tablet, dispersible tablet, enteric coatel tablets, particle, capsule, dripping pill, powder etc., mouth
Taking liquid preparation has oral solution, emulsion.
In one embodiment, the injection includes, but are not limited to small water needle, infusion, freeze-dried powder etc..
The preparation can be prepared according to the technique of this field routine.
It is also another object of the present invention to provide shown in (I) and/or (+)-(I) and/or (-)-(I) as described above
Pharmaceutical composition described in compound or its pharmaceutically acceptable salt or pharmaceutical composition as described above prepare it is anti-inflammatory and/
Or the application in anticancer drug.
In conclusion by adopting the above-described technical solution, the beneficial effects of the present invention are:
The present invention compared with the existing technology, has the following advantages and beneficial effect: (I) and/or (+)-(I) of the invention
And/or (-)-(I) compound represented is compound that is new, extracting from Spongia category sponge；The present invention passes through bioactivity
Test experiments show that above compound has anti-inflammatory or anti-tumor activity, can be used as and prepare anti-inflammatory or anti-tumor activity drug,
Also it can be used as lead compound to continue to modify to obtain having more preferably active anti-inflammatory or anti-tumor activity compound.
Detailed description of the invention
The NOESY map of Fig. 1 compound I
Specific embodiment
Below in conjunction with the embodiment of the present invention, technical scheme in the embodiment of the invention is clearly and completely described.
Based on the embodiments of the present invention, obtained by those of ordinary skill in the art without making creative efforts all
Other embodiments shall fall within the protection scope of the present invention.The variation of the invention of currently known or further exploitation is considered
It falls within the scope of the invention described herein and claimed below.
In the following example, optical activity is measured using JASCO P-2000 digital polarimeter.Using the ultraviolet -3600+ of Shimadzu
Spectrometer obtains ultraviolet spectra.Infrared light is determined using silent winged 50 Fourier Transform Infrared Spectrometer of Nicolet iS of match
Spectrum.High resolution mass spectrum data is obtained using Agilent 6210LC-ESI- Q/TOF.Use 300 nuclear magnetic resonance of Bruker AV
Spectrometer has obtained nmr spectrum data.CD spectrum is acquired with Jasco-Chirascan circular dichroism spectrometer.In Beijing
High performance liquid chromatography (Cosmosil C has been carried out respectively on logical wound and 1200 series of high efficiency liquid chromatograph of Agilent18-MS-II
Column, 5 μm, 20 × 250mm) and chiral high performance liquid chromatography (μm Amylose-1,5 μm, 4.6 × 250mm).Column layer
Analysis is carried out using silica gel (300-400 mesh, Qingdao Haiyang chemical company, Qingdao, China) and GE Sephadex LH-20.It uses
The silica gel plate (GF-254, Jiang You silica gel development corporation, Ltd., Yantai, China) of precoating carries out thin-layer chromatography.Phase chromatography-use
Methanol is chromatographically pure, and water is dual distilled water, other reagents are that analysis is pure.
Embodiment 1
Sponge (weight in wet base 8kg) is belonged to Spongia with 95% ethyl alcohol and carries out cold soaking extraction, total medicinal extract 313.0g is obtained, uses water
It is successively extracted with petroleum ether, chloroform and n-butanol after suspension, obtains each polar fraction.By chloroform extract extract (15.5
Gram) by silica gel column chromatography, use CHCl3/CH3OH (100:0~0:100) gradient elution obtains 8 fractions (fraction 1- 8).It will
Fraction 7 (1.5g) silicagel column CHCl3/CH3OH (100:0~0:100) gradient elution obtains 4 fraction (fraction 7-1~7-
4).With high performance liquid chromatography (flow velocity 6 ml/min, CH3OH/H2O=20:80 compound I (2.3) is isolated from fraction 7-1
mg).Compound I is passed through into chiral high performance liquid chromatography (flow velocity 1ml/min, CH3OH/H2O=75:25 (+)-I (t) is obtainedR1
=4.19min, 1.0mg) and (-)-I (tR2=4.83min, 1.2mg).
In NOESY spectrum, it can be observed that H-4 has NOE related to H-10/H-11, show that these hydrogen atoms are in ipsilateral,
And H-9 has that NOE is related to H-6/H-12/H-16b, shows that these hydrogen atoms and above-mentioned hydrogen atom, therefore, can in heteropleural
To determine the relative configuration (as shown in Figure 1) of compound I.The crystal for being suitable for x-ray diffraction experiment is obtained in experiment, into one
Step confirms that compound I is racemic modification.Compound I is separated by chiral high performance liquid chromatography, obtains compound (+)-I
(-)-I.By the measurement of polarimeter, the optical value for obtaining the two is respectively WithECD calculation method is then used, two are predicted
CD spectrum be compared with experimental spectrum, thus the absolute configuration of (+)-I He (-)-I has been determined.Therefore, (+)-I and (-)-
The absolute configuration of I is respectively 1R, 4S, 5S, 6S, 8S, 9R and 1S, 4R, 5R, 6R, 8R, 9S.
The physicochemical constant of obtained compound is as follows:
Colourless bulk (CH3OH) crystal；mp 287-288℃；HR-ESI-MS m/z 333.1675[M+Na]+(calcd
for C17H26O5Na:333.1672)；UVλmax (CH3OH):216nm；IRνmax:3420,1735,1371,1073,536cm-1
；13C and1H NMR is shown in Table 1.
(+)-I: white amorphous powder；CD (CH3OH)230(Δε+
1.50)nm。
(-)-I: white amorphous powder；CD (CH3OH)229(Δε-
2.52)nm。
1 compound of formula I of table1H (300MHz) with13C (75MHz) NMR data (CD3OD(δ,J in Hz)a)
aOverlapped signal does not indicate peak type in lists
Embodiment 2
Cytotoxic activity-experimental method
(1) logarithmic phase cell is taken to be laid in 96 orifice plates with the density in 5000, every hole, with corresponding culture medium, at 37 DEG C,
5%CO2Incubator in cultivate.
(2) agent-feeding treatment after 12h, medicine are first configured to 100 μM of mother liquor with DMSO, then are diluted to culture medium initial dense
Degree, is diluted to 10 concentration and carries out cell screening to it, by the culture medium culture cell containing drug in the form of changing liquid.
(3) after cultivating 72h, K562, A549, Hela, HT29, SK-BR-3, Huh7, PBL- are detected with the method for MTT
Sensibility of 2H3, PC3 and MCF7 cell to drug.MTT working solution is prepared with new culture medium, MTT is added to change the formation of liquid
Solution, 37 DEG C of incubation 10min.The absorbance of its 570nm is detected with microplate reader.
(4) IC of drug is calculated with GraphPad Prism 550。
Experimental result: compound (+)-I has certain cytotoxic activity, IC to MCF7 cell50 36.2μM。
Embodiment 3
Anti-inflammatory activity-experimental method
(1) luciferase reporter gene plasmid transient cotransfection HEK293 cell
HEK293 cell is cultivated in 96 orifice plates, when cell confluency degree is 50%~70% with NF- κ B luciferase report
PGL4.32 (hole 100ng/) and internal reference plasmid Renilla (hole 9.6ng/) cotransfection is accused, is made when transfection using liposome 2000
To assist transfection reagent.The plasmid of proper proportion and transfection reagent are placed in the culture medium of no FBS, are stood after mixing
15min, to ensure that plasmid is sufficiently combined with transfection reagent.Finally transfection liquid is added in 96 orifice plate of cell of preculture, in CO2
It is incubated for altogether in incubator more than for 24 hours.
(2) cell experiment grouping and administration
Cell experiment is divided into 4 groups, respectively blank group, model group, positive drug Dexamethasone group and sample sets.Cell each group
Pre-administration 6h, positive drug group give the dexamethasone of 10 μm of ol/L；Blank group, model group give fresh culture, and TNF-α is added
(whole mass concentration is 10ng/mL) modeling 6h, the lysate of collection are used for NF- κ B fluorescent inspection.
(3) NF- κ B luciferase reporter gene Activity determination
After the completion of administration, cell culture fluid is discarded, is washed cell 2 times with PBS (100 hole μ L/), discards PBS liquid, addition is matched
The cell pyrolysis liquid (20 hole μ L/) made, after shaken at room temperature 30min, it is bis- glimmering for NF- κ B that 15 μ L cell pyrolysis liquids are sucked out in every hole
The detection of light element enzyme reporter gene activity.20 μ L NF- κ B luciferase reporter plasmids are added into 15 μ L cell pyrolysis liquids
PGL4.32 (hole 100ng/) detection reagent after mixing gently, detects NF- κ B fluorescent value, adds 20 μ L internal reference luciferases
Detection reagent after mixing gently, detects Renilla fluorescent value.NF- κ B uciferase activity is calculated by formula, with relative fluorescence
Ratio indicates NF- κ B inhibiting rate.
Relative fluorescence ratio=NF- κ B fluorescent value/Renilla fluorescent value
Experimental result: when compound (-)-I concentration is 10 μ g/mL, inhibiting rate 38%.
The content of present invention merely illustrates claimed some specific embodiments, one of them or more skill
Documented technical characteristic can be combined with arbitrary one or more technical solutions in art scheme, these are combined and obtain
Technical solution also in the application protection scope, the technical solution just as obtained from these are combined is disclosed in the present invention
It is specifically recorded in content the same.
Claims (10)
1. a kind of compound or its pharmaceutically acceptable salt for extracting from Spongia and belonging to sponge, structural formula such as formula (I) institute
Show:
In formula,
R1The C for indicating H, optionally replacing1-C14Alkyl, the C optionally replaced1-C14Alkylthio group, the C optionally replaced1-C14Alkoxy or
C1-C14Alkenyl；
R2The C for indicating H, optionally replacing1-C14Alkyl, the C optionally replaced1-C14Alkylthio group, the C optionally replaced1-C14Alkoxy or
C1-C14Alkenyl；
R3The C for indicating H, optionally replacing1-C14Alkyl, the C optionally replaced1-C14Alkylthio group, the C optionally replaced1-C14Alkoxy or
C1-C14Alkenyl；
R4The C for indicating H, optionally replacing1-C14Alkyl, the C optionally replaced1-C14Alkylthio group, the C optionally replaced1-C14Alkoxy or
C1-C14Alkenyl.
2. extracting from compound or its pharmaceutically acceptable salt that Spongia belongs to sponge as described in claim 1, feature
It is, in formula (I), R1Indicate H, C1-C14Alkyl, halogenated C1-C14Alkyl, C1-C14Alkylthio group, halogenated C1-C14Alkylthio group, C1-
C14Alkoxy, halogenated C1-C14Alkoxy or C1-C14Alkenyl；
R2Indicate H, C1-C14Alkyl, halogenated C1-C14Alkyl, C1-C14Alkylthio group, halogenated C1-C14Alkylthio group, C1-C14Alkoxy, halogen
For C1-C14Alkoxy or C1-C14Alkenyl；
R3Indicate H, C1-C14Alkyl, halogenated C1-C14Alkyl, C1-C14Alkylthio group, halogenated C1-C14Alkylthio group, C1-C14Alkoxy, halogen
For C1-C14Alkoxy or C1-C14Alkenyl；
R4Indicate H, C1-C14Alkyl, halogenated C1-C14Alkyl, C1-C14Alkylthio group, halogenated C1-C14Alkylthio group, C1-C14Alkoxy, halogen
For C1-C14Alkoxy or C1-C14Alkenyl.
3. extracting from compound or its pharmaceutically acceptable salt that Spongia belongs to sponge as claimed in claim 2, feature
It is, in formula (I), R1Indicate H, C1-C6Alkyl, C1-C6Alkylthio group, C1-C6Alkoxy or C1-C6Alkenyl；R2Indicate H, C1-C6
Alkyl, C1-C6Alkylthio group, C1-C6Alkoxy or C1-C6Alkenyl；R3Indicate H, C1-C6Alkyl, C1-C6Alkylthio group, C1-C6Alcoxyl
Base or C1-C6Alkenyl；R4Indicate H, C1-C6Alkyl, C1-C6Alkylthio group, C1-C6Alkoxy or C1-C6Alkenyl；
Preferably, R1、R2、R3、R4It is each independently selected from H, methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl group, secondary
Butyl, tert-butyl, vinyl.
Extract from that Spongia belongs to the compound of sponge or its is pharmaceutically acceptable 4. as claimed in any one of claims 1-3
Salt, which is characterized in that formula (I) structure is as follows:
5. extracting from compound or its pharmaceutically acceptable salt that Spongia belongs to sponge as claimed in claim 4, feature
It is, formula (I) is (+)-(I) or (-)-(I), and (+)-(I), (-)-(I) structure are as follows:
6. it is a kind of it is according to any one of claims 1 to 5 extract from Spongia belong to sponge compound or its pharmaceutically may be used
The preparation method of the salt of receiving, which is characterized in that sponge is belonged to Spongia with solvent and is extracted, obtained extract is used
Column chromatography method separation is eluted, post-processes to obtain the compound for extracting from Spongia and belonging to sponge.
7. a kind of pharmaceutical composition, which is characterized in that extract from Spongia including such as of any of claims 1-4
Belong at least one of compound or its pharmaceutically acceptable salt of sponge；
Preferably, described pharmaceutical composition further includes pharmaceutically acceptable auxiliary material.
8. pharmaceutical composition as claimed in claim 7, which is characterized in that extracted shown in formula (I) in described pharmaceutical composition
The content of the compound or its pharmaceutically acceptable salt that belong to sponge from Spongia is the 1%-90% of pharmaceutical composition weight.
9. pharmaceutical composition as claimed in claim 7, which is characterized in that the dosage form of described pharmaceutical composition be oral preparation or
Injection；
Preferably, the oral preparation is selected from conventional tablet, dispersible tablet, enteric coatel tablets, particle, capsule, dripping pill, powder, oral solution
Or emulsion, the injection are small liquid drugs injection, infusion solution or freeze-dried powder.
Extract from that Spongia belongs to the compound of sponge or its is pharmaceutically acceptable 10. as described in any one in claim 1-5
Salt or pharmaceutical composition as claimed in any one of claims 7-9 are preparing the application in anti-inflammatory and/or anticancer drug.
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| CN1403469A (en) * | 2002-09-12 | 2003-03-19 | 中山大学 | Antineoplastic compound and its prepn and medicinal use |
| CN102229585A (en) * | 2011-04-26 | 2011-11-02 | 中国人民解放军第二军医大学 | [Gamma]-butyrolactone polyketone compounds with antitumor activities |
| WO2015116856A2 (en) * | 2014-01-29 | 2015-08-06 | City Of Hope | Farnesoid x receptor antagonists |
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| CN1403469A (en) * | 2002-09-12 | 2003-03-19 | 中山大学 | Antineoplastic compound and its prepn and medicinal use |
| CN102229585A (en) * | 2011-04-26 | 2011-11-02 | 中国人民解放军第二军医大学 | [Gamma]-butyrolactone polyketone compounds with antitumor activities |
| WO2015116856A2 (en) * | 2014-01-29 | 2015-08-06 | City Of Hope | Farnesoid x receptor antagonists |
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